A major nanotech advance in engineering multifunctional nanoparticles for imaging and therapeutic applications combines a short RNA (siRNA) to “silence” a specific gene with quantum dots and a “proton sponge” polymer coating to get the siRNA into the cell and released into the right compartment of the cell, rendering it both much more efficient and much less toxic to the cell. From the University of Washington, via AAAS EurekAlert “Gene silencer and quantum dots reduce protein production to a whisper“:

More than 15 years ago scientists discovered a way to stop a particular gene in its tracks. The Nobel Prize-winning finding holds tantalizing promise for medical science, but so far it has been difficult to apply the technique, known as RNA interference, in living cells.

Now scientists at the University of Washington in Seattle and Emory University in Atlanta have succeeded in using nanotechnology known as quantum dots to address this problem. Their technique is 10 to 20 times more effective than existing methods for injecting the gene-silencing tools, known as siRNA, into cells.

“We believe this is going to make a very important impact to the field of siRNA delivery,” said Xiaohu Gao, a UW assistant professor of bioengineering and co-author of a study published online this week in the Journal of the American Chemical Society [abstract].

“This work helps to overcome the longstanding barrier in the siRNA field: How to achieve high silencing efficiency with low toxicity,” said co-author Shuming Nie, a professor in the Wallace H. Coulter Department of Biomedical Engineering, jointly affiliated with the Georgia Institute of Technology and Emory University.

…This paper describes one of the first applications of quantum dots to drug delivery.

Each quantum dot was surrounded by a proton sponge that carried a positive charge. Without any quantum dots attached, the siRNA’s negative charge would prevent it from penetrating a cell’s wall. With the quantum-dot chaperone, the more weakly charged siRNA complex crosses the cellular wall, escapes from the endosome (a fatty bubble that surrounds incoming material) and accumulates in the cellular fluid, where it can do its work disrupting protein manufacture.

Key to the newly published approach is that researchers can adjust the chemical makeup of the quantum dot’s proton-sponge coating, allowing the scientists to precisely control how tightly the dots attach to the siRNA.